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Western University
Pathology 3240A
Craig Hall

Immunity and Immune Disorders ­ innate immune system recognizes molecular patterns o phagocytes (macrophages, neutrophils)  dendritic cells – also in adaptive immune system o natural killer cells ­ adaptive immune system  o cell mediated  recognizes specific antigens/epitopes o humoral  antibody mediated o cell types  lymphocytes • B cells • T cells The immune system ­ the body’s defense mechanism against microorganisms and their products (toxins) ­ two major components o innate immunity  born with, non specific  doesn’t require previous exposure to antigen  complement system  epithelial barrier  NK cells, phagocytes o adaptive  does require previous exposure  specific  B lymphocytes secrete antibodies  T lymphocytes • CD4 – helper T cells • CD8 – cytotoxic T cells Innate Immune System ­ major components o epithelial barrier  skin, mucosal surfaces o phagocytes   neutrophils, macrophages  recognize microbes via Toll­like receptors  ingest microbes and kill them with microbicidal substances o natural killer cells o complement system ­ Phagocytes o CD14 (LPS) receptor  Recognizes microbes based on pattern recognition  Toll­like receptor • When bound to receptors, produce mediators (cytokines,  etc.) which allows for amplification of immune response • Can also respond to different mediator • Allows for phagocytes to migrate to tissues where  inflammation is occurring, and cross the endothelium o Can phagocytose  Via phagocytic receptors  Once phagocytized, can destroy with lysozomal enzymes o Binds to receptor, engulfment  Recognized, attaches, then engulfment  Fuses with lysozomes once engulfed • to destroy the organism ­ NK Cells o Recognize and destroy virus infected cells as well as other damaged cells  and tumour cells o Recognize self via MHC class I molecules   Expressed on all HEALTHY cells – inhibitory signal o Damaged cells/tumour cells may not express normal MHC I  NK cells will destroy them o In addition damaged or stressed cells may bind to activating receptors on  NK cells o Thus they have the innate ability to lyse viral infected cells and tumour  cells without previous sensitization  o Function  When abnormal MHC I (damaged cell or infected) • No inhibitory signal • Can also have activating signal too  End result­ kills the cell ­ Complement System o Innate and adaptive immunity o Can be triggered to a microbe, mannose residues o Activated by proteolytic cascade o Inflammatory function  Recriutement and activation of neutrophils o Can trigger phagocytosis  Complement proteins can coat organisms, and will trigger  phagocytosis o Formation of membrane attack complex  Forms on surface of microbes, punches holes in membrane of the  organism o Adaptive immunity  Antibody­antigen interaction  Bound to surface of organism, can trigger activation of  complement cascade Adaptive Immune System ­ major components o lymphocytes (B cells, T cells) o antigen presenting cells  dendritic cells  macrophages  even B cells in some cases o human major histocompatibility complex (MHC) o complement system ­ Properties o Recognition: normal self, altered or injured self, non­self (foreign) o Specificity: ability to inactivate, destroy and remove invaders without  harming itself o Regulation: type, duration and intensity of reaction o Amplification: synergistic reactions between systems to reach optimal  effect (T and B cells, complement system, phagocytes) o Memory: remember the first exposure and accelerate reaction on second  exposure ­ Two Main Types o Humoral immunity  Antibody mediated (immunoglobin), targets extracellular microbes  Antibodies are produced by plasma cells and are specifically  directed ahainst a particular antigen  Antibodies can neutralize microbes, prmote their phagocytosis and  destruction and activate the complement system o Cell­mediated immunity  Reaction of T cells to attacked cell­associated microbes ­ T lymphocytes o Originate form primitive stem cell; yolf sac in the embryo and in the bone  marrow after birth o They mature in the Thymus and differentiate into:  Helper/inducer cells (CD4) • Help other cells types defend  Suppressor/cytotoxid (CD8) • Direct killing of infected cells o They constitute 60­70% of peripheral blood lymphocytes o The
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